Over exposure to sunlight can result in uncomfortable sunburn, premature aging of the skin, skin, wrinkles, loss of skin elasticity, dermatosis, and skin cancer. The most dangerous solar radiation is the ultraviolet (UV) radiation at wave lengths lower than 400 nm which includes both UV-A and UV-B radiation.
Sunscreen agents that primarily filter or absorb UV-A light are often referred to as UV-A absorbers. Similarly, sunscreen agents that primarily filter or absorb UV-B light are often referred to as UV-B absorbers. In general, the UV-A light refers to ultraviolet light having a wave length of 320-400 nm and UV-B light refers to ultraviolet light have a wave length of 280-320 nm.
A good UV absorbing chromophore should have excellent photostability, toxicological and dermatological acceptability, excellent heat stability, very good solubility in cosmetic solvents, compatibility with cosmetic bases, pH stability in the range of 4 to 9, processability into cosmetic formulations, compatibility with other ingredients of cosmetic formulations and with the packaging materials, no staining of textiles, no unpleasant odor, and it should be free of tackiness and have a low volatility.
Ultraviolet radiation can degrade photoactive substances by breaking down chemical bonds in the structure of a component such as a polymer. The absorbed radiation can excite the absorbing molecules and raise them to a higher energy level, which can be very reactive. If the molecule cannot be relaxed, bond cleavage and the formation of free radicals occurs. These free radicals can attack other molecules or components of tissue.
Accordingly, the performance of a photoactive compound or a combination of photoactive compounds in a sunscreen composition depends on these degradation processes, and the performance can degrade relatively quickly, for example, as is the case with avobenzone. Characterization of the rate of performance degradation requires expensive laboratory testing to determine the rate of loss of UV absorbance and a function of flux and duration. Moreover, a particularly difficult problem is presented when one photoactive compound in a sunscreen composition acts to increase the rate of photodegradation of another photoactive compound in the composition. Thus there is a need to immobilize in a segregated configuration different photoactive substances. The goal is to prevent a bimolecular reaction between two photoactive compounds when they come in contact, which lowers the threshold energy need to raise a photoactive compound to its excited state. For example, when avobenzone is combined with octyl methoxycinnamate a bimolecular pathway leads to the rapid photodegradation of both the dibenzoylmethane derivative and the octyl methoxycinnamate.
Most UV absorbing chromophores used in sunscreen compositions are monomeric compounds, and thus there is the inherent risk that such compounds penetrate the skin barrier, which is highly undesirable.
The present invention relates generally to compositions comprising chemical groups possessing a light absorbing or blocking function bonded to chemical groups possessing a tissue bonding function and methods of making and applying such compositions to mammalian skin. In particular, the present invention is directed towards compositions useful in the cosmetic or sunscreen industry in which one aspect prevents tissue infiltration, another aspect promotes permanence, and yet another aspect is photobiologically active. More particularly, the present invention details structures which are localized to the surface of tissue and minimize the depth to which potentially sensitizing components penetrate tissue, and other structures which bond to particular cellular types characteristic of a tissue surface, and other therapeutic structures which are optionally detachably connected to said bonding and infiltration preventing structures, in combination or separately, wherein said therapeutic structures are released from the skin surface over a selectable period of time.
Therefore, there is a demand for sunscreens which meet the above requirements and which, in particular, have a reduced risk of penetrating the skin and the components of which are immobilized against contact. The sunscreens should have comparably, preferably better properties than the sunscreens of the prior art, in particular they should combine a high SPF with a low risk of skin penetration, and a means for maintaining a desired SPF factor for a duration longer than the average expected exposure interval.
For example, a particularly advantageous family of UV-A screens is constituted by dibenzoylmethane derivatives, in particular 4-tert-butyl-4′-methoxydibenzoyl methane, which have intrinsically good absorbing powers. Unfortunately, it has been discovered that dibenzoylmethane derivatives are relatively sensitive to ultraviolet radiation (in particular UV-A), i.e., more precisely, they have an annoying tendency to degrade at a greater or lesser rate under the action thereof. This substantial lack of photochemical stability of dibenzoylmethane derivatives to the ultraviolet radiation to which they are by their very nature intended to be subjected cannot guarantee constant protection during prolonged exposure to the sun, and repeated applications at regular, close intervals have to be made by the consumer to effectively protect the skin against UV radiation.
Heretofore, a number of patents have disclosed sun block compositions, compositions containing biologically active molecules and combinations. The relevant portions of which may be briefly summarized as follows:
U.S. Pat. No. 8,128,913 describes a sunscreen composition comprising a skin bonding polymer composition comprising a hydrophobic polymer/hydrophilic polymer adduct, at least one sunscreen active agent comprising a UV-A absorber, and water in an amount of affected to provide a the composition with the texture suitable for application to skin.U.S. Pat. No. 8,025,867 describes a photostable, topically applicable cosmetic/dermatological compositions contain at least one dibenzoylmethane compound UV-A sunscreen and at least one merocyanine sulfone compound.U.S. Pat. No. 7,988,953 describes a conjugate comprising a hyperbranched polymer covalently bonded to at least three UV absorbing chromophores having an UV absorptionU.S. Pat. No. 7,981,402 describes polymers containing one or more novel photoactive moieties, sunscreen compositions including a mixture of a photoactive compound and a polymer containing one or more photoactive moieties.U.S. Pat. No. 7,910,090 describes a base composition that allows for the formulation of non-irritating cosmetic and/or dermatological compositions.U.S. Pat. No. 7,897,779 describes novel 1,4-dihydropyridine derivatives and novel cosmetic or dermatological sunscreen compositions containing these derivatives.U.S. Pat. No. 7,892,524 describes an organic sunscreen agent dispersed within a condensation polymerized resin having carboxylic acid groups.U.S. Pat. No. 7,799,317 describes polymers containing one or more novel photoactive moieties, sunscreen compositions including a mixture of a photoactive compound and a polymer containing one or more photoactive moieties.U.S. Pat. No. 7,790,202 describes a multi-purpose skin composition which functions as a sunscreen, an anti-perspirant, an insect/pest repellant and/or an antiseptic.U.S. Pat. No. 7,674,764 describes a composition for controlled release of an active material such as a fragrance, sunscreen, vitamin or biocide in a product.U.S. Pat. No. 7,534,421 describes a stable, topically applicable cosmetic/dermatological sunscreen compositions, well suited for the UV-photoprotection of human skin/keratinous materials, containing a thus effective amount of at least one novel s-triazine compound bearing at least one para-aminobenzalmalonic salt substituent.U.S. Pat. No. 7,416,721 describes a sunscreen compositions having improved comfort after applicationU.S. Pat. No. 7,384,916 describes methods for treating aging and photodamaged skin employing topical application of compositions which comprise at least one peptide manganese complex.U.S. Pat. No. 7,374,749 describes amino substituted hydroxyphenyl benzophenone derivatives.U.S. Pat. No. 7,326,408 describes topical sunscreens obtained by combining a topical sunscreen agent in a formulation containing an antibacterial medication such as azelaic acid or an antibiotic.U.S. Pat. No. 7,326,407 describes a stable, topically applicable cosmetic/dermatological sunscreen compositions, well suited for the UV-photoprotection of human skin/keratinous materials, containing an effective amount of at least one novel amine, amide, sulphonamide or carbamate substituted benzalmalonic salt compound.U.S. Pat. No. 7,235,587 describes diesters containing two crylene or fluorene moieties, sunscreen compositions containing the same, and methods of photostabilizing a sunscreen composition.U.S. Pat. No. 7,153,494 describes a topically applicable photostable sunscreen/photoprotective compositions contain at least one dibenzoylmethane UV-sunscreen and an effective photostabilizing amount therefor of at least one amphiphilic block copolymer which comprises at least one nonionic hydrophilic polymer block and at least one hydrophobic polymer block, formulated into a topically applicable, cosmetically acceptable medium.U.S. Pat. No. 6,284,258 describes compounds that are two-part molecules, and compositions containing such compounds, in which one part is designed to become covalently bonded to the skin (bonding agent) and the other part (a characteristic use agent) is designed to impart some characteristic use, such as emolliency, moisturizing effect, anti-acne, anti-wrinkle, anti-pain, antimicrobial, antifungal, antiviral, anti-irritation, skin tanning and skin lightening effects, extended protection of the skin (e.g., from ultraviolet light, by incorporation of a sunscreen component.U.S. Pat. No. 5,951,967 describes a multi-phase sunscreen agent, characterized by at least two phases that are liquid to pasty or gelatinous and separate from each other spontaneously within seconds to less than ten minutes after a brief and gentle mixing process lasting less than one minute without any essential application of force, where at least one phase contains a UV filter.U.S. Pat. No. 4,844,884 describes cosmetic sunscreen products which contain a tyrosine derivative.A typical topical sunscreen has no mechanism for chemically fixating to the exterior tissue layers comprising skin. Compositions relying on hydrophobicity are commonly mechanically wiped away by towels and the like. Compositions that diffuse into skin typically do not penetrate deeply and rely on a concentration gradient where the location of maximum concentration is at the skin surface. As the concentration at the skin surface is depleted by mechanical dissociation, the concentration gradient reverses direction, wherein the higher concentration within tissue causes the infiltrated composition to begin diffusing to the skin surface. Accordingly, such compositions do not reside long within the skin in physiologically significant concentration, typically less than a few hours. And the allowance of skin penetration to the level of living tissue can result in sensitization, allergic reaction, and immunological response.There is a need for augmenting tissue residence time of dermatological preparations. Therefore it is an object of the present invention to provide molecular species for delivering dermatologically active molecules to tissue comprising one or more of the following: a) the formation of a bond between said dermatological molecule and a specific layer of skin, b) the localization of said dermatological molecules to a specific layer of skin, and c) the sequestration of multiple photoactive components on a single molecule in a manner that prevents them from interacting in a degradational mode.It is further an object of the present invention to provide methods and compositions for modifying a tissue surface. For example, bonding protective molecules so as to protect the underlying tissue layers from solar radiation, allergens, microbes, chemical toxins and the like. It is further an object of the present invention to provide methods and compositions for conditioning a surface. For example, one or more of the steps of improving the resiliency or feel of a tissue layer, reducing the surface tension between topical preparation and tissue structures, modifying the electrical charge or energy state of a tissue structure, modifying the nucleophilicity of a tissue structure including modifying its hydrophobicity and oleophobicity. It is further an object of the present invention to provide methods and compositions for facilitating release of a biologically active substance at a specific tissue layer. For example, adding one or more functional groups which bond to a tissue layer in a biologically inactive state and are subsequently released by local metabolic and chemical processes, or adding one or more enhancers which bond to a tissue surface and are required for activation or release of a biologically active substance.It is further an object of the present invention to provide methods and compositions for increasing the functionality of an enhancer molecule to enable a multiplicity of biologically active processes. For example, adding one or more tissue-reactive functional groups, increasing the number and density of a tissue-reactive functional group, reducing the mean molecular weight of a carrier molecule while maintaining or increasing the number of functional groups per mean molecular weight, and adding an optional tractor functionality to a dermatological composition which creates a reverse gradient and biological functionality which bonds to an adverse molecule and transports said bonded pair to the skin surface.There is a need for dermatological preparations comprising sunscreens with a palliative component which provides a rapid initial bolus of biologically active molecules, wherein the reactions responsible for this first curative state do not fully fixate the composition and leave it transportable and in a tissue-reactive state, and subsequently this tissue-reactive state and tissue bonding functionality persists for some time to enable deep penetration.Finally, it is an object of the present invention to provide tissue bonding systems comprised of two distinct phases wherein the second phase releases photobiologically active components from the tissue at a desired time.It is further an object of the present invention that the first tissue bonding phase reaches a high fixation state quickly while leaving most of its biologically active functionality unchanged and remains in that state for an extended period of time.It is another object of the present invention that the second biologically active phase modifies tissue and provides biological functionality for an extended period of time.